Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 31, Pages 24131-24140Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.120212
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Funding
- National Institutes of Health [AI-077538]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico e Instituto Nacional de Ciencia e Tecnologia de Vacinas do Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil
- Ellison Medical Foundation to the Center for Tropical and Emerging Global Diseases
- American Heart Association
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Target of rapamycin (TOR) kinases are highly conserved protein kinases that integrate signals from nutrients and growth factors to coordinate cell growth and cell cycle progression. It has been previously described that two TOR kinases control cell growth in the protozoan parasite Trypanosoma brucei, the causative agent of African trypanosomiasis. Here we studied an unusual TOR-like protein named TbTOR-like 1 containing a PDZ domain and found exclusively in kinetoplastids. TbTOR-like 1 localizes to unique cytosolic granules. After hyperosmotic stress, the localization of the protein shifts to the cell periphery, different from other organelle markers. Ablation of TbTOR-like 1 causes a progressive inhibition of cell proliferation, producing parasites accumulating in the S/G(2) phase of the cell cycle. TbTOR-like 1 knocked down cells have an increased area occupied by acidic vacuoles, known as acidocalcisomes, and are enriched in polyphosphate and pyrophosphate. These results suggest that TbTOR-like 1 might be involved in the control of acidocalcisome and polyphosphate metabolism in T. brucei.
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